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1.
J Clin Invest ; 132(11)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35642633

RESUMO

Since researchers first began to uncover the mechanisms underlying allogeneic transplantation, the focus has been on T cells. T cells are a major instigator of graft-versus-host disease (GVHD). The clear association between GVHD occurrence and subsequent reduction in relapse supported concentrating on T cells as the masterminds behind graft-versus-tumor (GVT) effects. Recently, an alternative mediator of GVT has taken center stage: natural killer (NK) cells. Part of the appeal of NK cells is their potential to provide antitumor immunity without GVHD. Donor lymphocyte infusion has been the predominant treatment of relapse after allogeneic transplant, but the mix of lymphocytes includes CD8+ T cells and, consequently, a substantial risk for GVHD. In this issue of the JCI, Shapiro and colleagues developed an adoptive NK cell transfer platform to treat relapse after haploidentical allogeneic transplant. The study demonstrated safety, sought to determine resistance mechanisms, and provided avenues for future research.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Imunoterapia Adotiva , Células Matadoras Naturais , Recidiva
2.
Indian J Cancer ; 59(1): 4-11, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35645049

RESUMO

Acute lymphoblastic leukemia (ALL) is the malignant transformation of lymphoid progenitors that affects both children and adults. Although the outcome of pediatric patients has been improved dramatically, there are still many challenges in the treatment of adults. Patients with primary resistant or relapsed disease have the worst outcome and despite the administration of intensified multi-agents chemotherapies, the outcome of this group remains very poor. Accordingly, the development of novel therapeutic options is considered necessary. Having a comprehensive insight into the pathophysiology of ALL and aberrant signaling pathways is crucial for introducing effective targeted therapies. Combination therapies with new drugs and innovative targeted therapies with the aim of affecting the main aberrant signaling pathways in the disease are considered as new approaches. Here we tried to have a comprehensive review on the potential molecular targets in the treatment of refractory/relapsed ALL and the current therapeutic agents.


Assuntos
Antineoplásicos Imunológicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Criança , Humanos , Terapia de Alvo Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Recidiva
3.
PLoS One ; 17(6): e0268963, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35700185

RESUMO

Although hematopoietic stem cell transplantation (HCT) is the only curative treatment for acute myeloid leukemia (AML), it is associated with significant treatment related morbidity and mortality. There is great need for predictive biomarkers associated with overall survival (OS) and clinical outcomes. We hypothesized that circulating metabolic, inflammatory, and immune molecules have potential as predictive biomarkers for AML patients who receive HCT treatment. This retrospective study was designed with an exploratory approach to comprehensively characterize immune, inflammatory, and metabolomic biomarkers. We identified patients with AML who underwent HCT and had existing baseline plasma samples. Using those samples (n = 34), we studied 65 blood based metabolomic and 61 immune/inflammatory related biomarkers, comparing patients with either long-term OS (≥ 3 years) or short-term OS (OS ≤ 1 years). We also compared the immune/inflammatory response and metabolomic biomarkers in younger vs. older AML patients (≤30 years vs. ≥ 55 years old). In addition, the biomarker profiles were analyzed for their association with clinical outcomes, namely OS, chronic graft versus host disease (cGVHD), acute graft versus host disease (aGVHD), infection and relapse. Several baseline biomarkers were elevated in older versus younger patients, and baseline levels were lower for three markers (IL13, SAA, CRP) in patients with OS ≥ 3 years. We also identified immune/inflammatory response markers associated with aGVHD (IL-9, Eotaxin-3), cGVHD (Flt-1), infection (D-dimer), or relapse (IL-17D, bFGF, Eotaxin-3). Evaluation of metabolic markers demonstrated higher baseline levels of medium- and long-chain acylcarnitines (AC) in older patients, association with aGVHD (lactate, long-chain AC), and cGVHD (medium-chain AC). These differentially expressed profiles merit further evaluation as predictive biomarkers.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Idoso , Quimiocina CCL26 , Humanos , Imunidade , Leucemia Mieloide Aguda/terapia , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante
4.
Stem Cell Res ; 62: 102828, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35679759

RESUMO

Multiple sclerosis (MS) is a complex neuroinflammatory/degenerative disease of the central nervous system (CNS) that results in the formation of demyelinated lesions and axon degeneration. MS aetiology is complex, with genetics estimated to account for ∼48% of MS risk (International Multiple Sclerosis Genetics Consortium, 2019). Despite this, families with a high incidence of MS are rare. We have generated four induced pluripotent stem cell (iPSC) lines from individuals with relapsing-remitting and secondary progressive MS within a single family. The generation of disease-specific iPSC lines from multiple members of a single family will facilitate MS genetic and functional studies.


Assuntos
Células-Tronco Pluripotentes Induzidas , Esclerose Múltipla , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Esclerose Múltipla/metabolismo , Recidiva
5.
Addict Behav ; 133: 107371, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35691124

RESUMO

BACKGROUND AND AIMS: The number of patients with gambling disorder (GD) whose gambling preference is sports betting is increasing. However, their clinical profile and their responses to psychological treatments -compared to patients with other forms of gambling- have not been thoroughly studied. Therefore, the aims of this study were: (1) to compare the clinical characteristics of GD patients whose primary gambling activity was sports betting (SB+; n = 113) with GD patients with other primary gambling activities (SB-; n = 1,135); (2) to compare treatment outcomes (dropout and relapses) between SB + and SB- patients; and (3) to explore relationships between specific variables (GD severity, psychological distress and personality features) and treatment outcome in SB + and SB- GD patients, through correlation models and path-analysis. METHODS: The cognitive behavioral treatment consisted of 16 weekly sessions. Personality features, psychopathology, and sociodemographic and clinical factors were assessed. RESULTS: The SB + group included higher proportions of younger patients who were single and had higher educational levels, older ages of GD onset, and greater GD severities. Regarding treatment outcomes, the dropout rate was lower in the SB + group, and no between-group differences were found regarding relapse. Dropout within the SB + group was related to being unemployed, and relapse was related to being unmarried and experiencing more psychological distress. DISCUSSION AND CONCLUSION: The differences between SB + and SB- GD patients suggest that GD patients with sports-betting problems may benefit from tailored therapeutic approaches.


Assuntos
Terapia Cognitivo-Comportamental , Jogo de Azar , Angústia Psicológica , Esportes , Jogo de Azar/psicologia , Jogo de Azar/terapia , Humanos , Recidiva , Esportes/psicologia
6.
PLoS One ; 17(6): e0268290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35709199

RESUMO

OBJECTIVE: Prevention of tuberculosis (TB) recurrence is an important issue in TB control. South Korea, a country with a high average income, has been challenged with an intermediate burden of TB. We aimed to estimate the TB recurrence rate after successful completion of the first anti-TB chemotherapy, and to identify the risk factors for the TB recurrence by focusing on co-morbidities and behavioral factors. METHODS: This is a population-based cohort study using data from the National Health Insurance (NHI) database between 2002 and 2013. Newly diagnosed TB patients were identified using the classification of disease codes and prescription records. Final analytical subjects included people who successfully completed the first anti-TB chemotherapy. The primary outcome measure was recurrent TB 6-month after the first treatment completion. A set of associated risk factors, including demographic characteristics, co-morbidities, and health behavior factors were analyzed using Cox regression analysis. RESULTS: Among 5,446 TB patients, 2,226 (40.1%) completed the first anti-TB treatment. During the follow-up period, 150 (6.7%) patients had TB recurrence, and the crude recurrent rate was 22.6 per 1000 person-years. The majority of recurrence cases (89%) occurred within the first 2-year period. The major findings show that participants who are male (adjusted HR (aHR) = 1.81, at a 95% CI, range: 1.11-2.94), older in age (aHR = 1.07, at a 95% CI, range: 1.00-1.14), have a lower income (aHR = 1.96, at a 95% CI, range: 1.10-3.48) and who are underweight (aHR = 1.92, at a 95% CI, range 1.15-3.20) were at higher risks for TB recurrence. CONCLUSION: People who have risk factors for recurrent TB need to improve treatment compliance through more effective TB management, and follow-up observation for one or two years after the treatment completion.


Assuntos
Antituberculosos , Tuberculose , Antituberculosos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
7.
Sci Rep ; 12(1): 10048, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710924

RESUMO

The global emergence of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli), mainly causing urinary tract infections (UTI), is of great concern. Almost one third of patients with UTI, develop recurrent UTI (RUTI). We followed 297 patients for one year after their first episode of UTI due to ESBL-E. coli. Our aim was to evaluate the impact of the globally dominant sequence type (ST)131 clone and its clades, on the risk of subsequent recurrences with ESBL-E. coli. Isolates from patients developing RUTI (68/297) were compared with those from patients with sporadic UTI (SUTI, 229/297). No association was found between RUTI and the two most prevalent phylogroups B2 and D, blaCTX-M genes, or resistance profile. Half of the patients with RUTI were infected with ST131 isolates. Clade C2 were in dominance (50/119) among ST131 isolates. They were more common in patients with RUTI than SUTI (28% vs 13%) and multivariate analysis showed an increased odds-ratio (OR = 2.21, p = 0.033) for recurrences in patients infected with these isolates as compared to non-ST131 isolates. Detecting specific biomarkers, as ST131 clade C2, in ESBL-E. coli UTI isolates may aid in prediction of RUTI and improve diagnostics and care of patients with a risk of ESBL-E. coli recurrences.


Assuntos
Infecções por Escherichia coli , Infecções Urinárias , Antibacterianos , Células Clonais , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Recidiva , Infecções Urinárias/epidemiologia , beta-Lactamases/genética
8.
Can J Gastroenterol Hepatol ; 2022: 4209442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711246

RESUMO

Clostridium difficile is a Gram-positive bacillus with fecal-oral transmission and is currently one of the most common nosocomial infections worldwide, which was renamed Clostridioides difficile in 2016. Clostridioides difficile infection (CDI) is a prevalent infection in cirrhosis and negatively affects prognosis. This study aimed to provide a concise review with clinical practice implications. The prevalence of CDI in cirrhotic patients increases, while the associated mortality decreases. Multiple groups of risk factors increase the likelihood of CDI in patients with cirrhosis, such as antibiotic use, the severity of cirrhosis, some comorbidities, and demographic aspects. Treatment in the general population is currently described in the latest guidelines. In patients with cirrhosis, rifaximin and lactulose have been shown to reduce CDI risk due to their modulatory effects on the intestinal flora, although conflicting results exist. Fecal microbiota transplantation (FMT) as a treatment for the second or subsequent CDI recurrences has demonstrated a good safety and efficacy in cirrhosis and CDI. Future validation in more prospective studies is needed. Screening of asymptomatic patients appears to be discouraged for the prevention currently, with strict hand hygiene and cleaning of the ward and medical equipment surfaces being the cornerstone of minimizing transmission.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/prevenção & controle , Transplante de Microbiota Fecal/métodos , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Recidiva , Rifaximina , Resultado do Tratamento
9.
Front Immunol ; 13: 901165, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711452

RESUMO

Objective: The aim of this study is to assess the peripheral immune system of newly diagnosed patients with relapsing remitting multiple sclerosis (RRMS) and compare it to healthy controls (HC). Methods: This cross-sectional study involves 30 treatment-naïve newly diagnosed patients with RRMS and 33 sex- and age-matched HC. Peripheral blood mononuclear cells were analyzed regarding: i) thymic function surrogates [T cell receptor excision circles (TRECs) and recent thymic emigrants (RTEs)]; ii) naïve and memory CD4+ and CD8+ T cells subsets; iii) T helper (Th) phenotype and chemokine receptors expression on CD8+ T cells subsets; iv) regulatory T cell (Tregs) phenotype; and exclude expression of activating/inhibitory receptors by natural killer (NK) and NKT cells. Analyses were controlled for age, sex, and human cytomegalovirus (HCMV) IgG seroprevalence. Results: Newly diagnosed patients with RRMS and HC have equivalent thymic function as determined by similar numbers of RTEs and levels of sjTRECs, DJßTRECs, and sj/DJßTREC ratio. In the CD8+ T cells compartment, patients with RRMS have a higher naive to memory ratio and lower memory cell counts in blood, specifically of effector memory and TemRA CD8+ T cells. Interestingly, higher numbers and percentages of central memory CD8+ T cells are associated with increasing time from the relapse. Among CD4+ T cells, lower blood counts of effector memory cells are found in patients upon controlling for sex, age, and anti-HCMV IgG seroprevalence. Higher numbers of CD4+ T cells (both naïve and memory) and of Th2 cells are associated with increasing time from the relapse; lower numbers of Th17 cells are associated with higher MS severity scores (MSSS). Patients with RRMS have a higher percentage of naïve Tregs compared with HC, and lower percentages of these cells are associated with higher MSSS. Percentages of immature CD56bright NK cells expressing the inhibitory receptor KLRG1 and of mature CD56dimCD57+ NK cells expressing NKp30 are higher in patients. No major alterations are observed on NKT cells. Conclusion: Characterization of the peripheral immune system of treatment-naïve newly diagnosed patients with RRMS unveiled immune features present at clinical onset including lower memory T cells blood counts, particularly among CD8+ T cells, higher percentage of naïve Tregs and altered percentages of NK cells subsets expressing inhibitory or activating receptors. These findings might set the basis to better understand disease pathogenesis.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Linfócitos T CD8-Positivos , Estudos Transversais , Humanos , Imunoglobulina G , Leucócitos Mononucleares/metabolismo , Recidiva , Estudos Soroepidemiológicos , Linfócitos T Reguladores
10.
Cardiovasc Ther ; 2022: 6993904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692374

RESUMO

Background: Circulating galectin-3 (Gal-3) and aldosterone (ALD) are involved in fibrosis and inflammation. However, their potential value as predictors of atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) is unknown or controversial. Therefore, the aim of this study was to assess the relationship between baseline Gal-3, ALD levels, and AF recurrence in patients performing RFCA. Methods: 153 consecutive patients undergoing RFCA were included. Gal-3 and ALD were measured at baseline. Univariate and multivariate Cox regressions were performed to determine the predictors of AF recurrence. Receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) curve were used to assess the value of predictors. Results: There were 35 (22.88%) cases of AF recurrence after RFCA. The recurrence group had significantly higher preoperative serum levels of Gal-3 and ALD than the nonrecurrence group. Univariate and multivariate analysis showed that Gal-3 (HR = 1.28, 95% CI: 1.04-1.56, p = 0.02) and ALD (OR = 1.02, 95% CI: 1.00-1.03, p < 0.03) were significantly associated with AF recurrence after RFCA. The area under the curve (AUC) of preoperative serum Gal-3, ALD, and 2 combined to predict the recurrence of AF patients after RFCA was 0.636, 0.798, and 0.893, respectively, while sensitivity was 65.32%, 71.69%, and 88.61%, respectively and specificity was 77.46%, 78.53%, and 86.0%, respectively. Patients with Gal-3 above the cutoff value of 14.57 pg/ml had higher frequent AF recurrence than the patients with Gal - 3 ≤ 14.57 pg/ml (35% vs. 12%, p < 0.001) during a follow-up. Meanwhile, patients with ALD above the cutoff value of 243.61 pg/ml also had a higher AF recurrence rate than those with ALD ≤ 243.61 pg/ml (37% vs. 11%, p < 0.001) during a follow-up. The recurrence rate in patients with Gal - 3 > 14.57 pg/ml + ALD > 243.61 pg/ml was higher than that in patients with baseline Gal - 3 > 14.57 pg/ml or ALD > 243.61 pg/ml and patients with Gal - 3 ≤ 14.57 pg/ml + ALD ≤ 243.61 pg/ml (57% vs. 14% vs. 9%, p < 0.01, respectively). Conclusion: AF recurrence after RFCA had higher baseline Gal-3 and ALD levels, and higher preoperative circulating Gal-3 and ALD levels were independent predictors of AF recurrence for patients undergoing RFCA, while combination of preoperative Gal-3 and ALD levels has higher prediction accuracy.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Aldosterona , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Galectina 3 , Humanos , Recidiva , Fatores de Risco , Resultado do Tratamento
11.
PLoS One ; 17(6): e0264797, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35687598

RESUMO

Extinction learning is central to exposure-based behavioral therapies for reducing fear and anxiety in humans. However, patients with fear and anxiety disorders are often resistant to extinction. Moreover, trauma and stress-related disorders are highly prone to relapse and are twice as likely to occur in females compared to males, suggesting that females may be more susceptible to extinction deficits and fear relapse phenomena. In this report, we tested this hypothesis by examining sex differences in a stress-induced extinction learning impairment, the immediate extinction deficit (IED), and renewal, a common form of fear relapse. In contrast to our hypothesis, there were no sex differences in the magnitude of the immediate extinction deficit in two different rat strains (Long-Evans and Wistar). However, we did observe a sex difference in the renewal of fear when the extinguished conditioned stimulus was presented outside the extinction context. Male Wistar rats exhibited significantly greater renewal than female rats, a sex difference that has previously been reported after appetitive extinction. Collectively, these data reveal that stress-induced extinction impairments are similar in male and female rats, though the context-dependence of extinction is more pronounced in males.


Assuntos
Extinção Psicológica , Caracteres Sexuais , Animais , Medo , Feminino , Humanos , Masculino , Ratos , Ratos Long-Evans , Ratos Wistar , Recidiva
12.
Medicine (Baltimore) ; 101(23): e29431, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35687780

RESUMO

RATIONALE: Since mass-scale severe acute respiratory syndrome coronavirus 2 vaccination, there have been case reports of several immune-mediated reactions, including new-onset and flares of glomerular disorders following immunization with mRNA coronavirus disease 2019 vaccines. Here, we report two cases, the first to our knowledge, of relapsing cryoglobulinemic vasculitis with new-onset severe renal involvement following mRNA coronavirus disease 2019 vaccination. PATIENT CONCERNS: The relapse of the cutaneous and the new onset of severe renal involvement of cryoglobulinemic vasculitis occurred three weeks after the second dose of the mRNA Moderna coronavirus disease 2019 vaccination and two days after the first dose of mRNA Pfizer coronavirus disease 2019 vaccination in the first and second patient, respectively. DIAGNOSIS: Kidney biopsies were performed. The first pacient's kidney biopsy showed a membranoproliferative pattern of glomerular injury with extensive mesangial and endocapillary hypercellularity, while severe endothelial swelling, loss of fenestrations and widening of subendothelial space were identified by electron-microscopy. The second patient's kidney biopsy was consistent with cryoglobulin associated membrano-proliferative pattern of glomerular injury. INTERVENTIONS: Our patients were managed with a combination of immunosuppressants consisting of corticosteroids, Cyclophosphamide and Rituximab with a favourable outcome at the end of the induction period. OUTCOMES: Clinical and immunological response was achieved in both patients after four months of follow-up. LESSONS: The temporal association of the relapse of the cryoglobulinemic vasculitis to mRNA coronavirus disease 2019 vaccination suggest that the vaccine might have been a trigger for the reactivation of the disease in our cases. This possible association should be acknowledged by physicians in order to provide optimal monitoring and treatment in case of reactivation of the disease post-immunization.


Assuntos
COVID-19 , Crioglobulinemia , Nefropatias , Vasculite , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Doença Crônica , Crioglobulinemia/complicações , Humanos , Nefropatias/complicações , RNA Mensageiro , Recidiva , Vacinação/efeitos adversos , Vasculite/complicações
13.
Trials ; 23(1): 483, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35689289

RESUMO

BACKGROUND: Treatment of superficial venous reflux has been shown to improve ulcer healing time and reduce the risk of ulcer recurrence. Terminal ablation of the reflux source (TIRS) is an alternative to formal endovenous ablation or surgery which can be performed by injecting sclerosant foam into the peri-ulcer plexus of the veins. TIRS has been shown to be successful and in our experience is the option preferred by many patients, when offered as an alternative to axial ablation (AA). AIM: To determine if the proportion of ulcers healed within 6 months of endovenous treatment differs between patients undergoing AA of varicose veins or TIRS by peri-ulcer foam sclerotherapy. METHODS: AAVTIRS is an assessor-blinded randomised controlled trial. Patients will be recruited from a dedicated ulcer clinic in Roscommon University Hospital and from the vascular surgical clinics in University Hospital Galway. All patients attending the ulcer clinic will be screened for eligibility. RANDOMISATION: Random computer-generated sequence is stratified by ulcer size. Allocation will be concealed using sealed opaque envelopes. BLINDING: Assessors reviewing wounds at follow -p visits will be blinded to patient allocation. PRIMARY ENDPOINT: The proportion of ulcers healed within 6 months of enrolment. DISCUSSION: This will be the first time that TIRS has been evaluated with a properly powered randomised trial in the setting of venous ulcer management. Streamlining the management of venous ulcers has broad health economic benefits. If it is found that TIRS is superior or non-inferior to AA, then a less expensive, less invasive injection can be offered as an alternative to AA in an attempt to encourage the healing of venous ulcers. If AA is found to be superior to TIRS, then this would suggest that all patients undergoing ablation in the management of venous ulcers should have their superficial reflux fully treated, building on the evidence of the EVRA trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484168. Registered on 23 July 2020.


Assuntos
Úlcera Varicosa , Varizes , Humanos , Recidiva , Escleroterapia/efeitos adversos , Resultado do Tratamento , Úlcera/etiologia , Úlcera Varicosa/diagnóstico , Úlcera Varicosa/terapia , Varizes/terapia
14.
Clin J Pain ; 38(7): 484-491, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35686578

RESUMO

OBJECTIVES: Theoretical models suggest that anxiety, pain intensity, and pain catastrophizing are implicated in a cycle that leads to heightened fear of cancer recurrence (FCR). However, these relationships have not been empirically examined. The objective of this study was to examine the relationships between anxiety symptoms, pain intensity, pain catastrophizing, and FCR in childhood cancer survivors and their parents and to examine whether pain catastrophizing predicts increased FCR beyond anxiety symptoms and pain intensity. METHODS: The participants were 54 survivors of various childhood cancers (Mage=13.1 y, range=8.4 to 17.9 y, 50% female) and their parents (94% mothers). Children reported on their pain intensity in the past 7 days. Children and parents separately completed measures of anxiety symptoms, pain catastrophizing, and FCR. RESULTS: Higher anxiety symptoms were associated with increased pain intensity, pain catastrophizing, and FCR in childhood cancer survivors. Higher anxiety symptoms and pain catastrophizing, but not child pain intensity, were associated with FCR in parents. Hierarchical linear regression models revealed that pain catastrophizing explained unique variance in both parent (ΔR2=0.11, P<0.01) and child (ΔR2=0.07, P<0.05) FCR over and above the effects of their own anxiety symptoms and child pain. DISCUSSION: The results of this study provides novel data on the association between pain and FCR and suggests that a catastrophic style of thinking about pain is more closely related to heightened FCR than one's anxiety symptoms or the sensory pain experience in both childhood cancer survivors and their parents. Pain catastrophizing may be a novel intervention target for survivors and parents struggling with fears of recurrence.


Assuntos
Sobreviventes de Câncer , Neoplasias , Criança , Medo , Feminino , Humanos , Masculino , Neoplasias/complicações , Dor/etiologia , Recidiva , Sobreviventes
15.
Dental Press J Orthod ; 27(2): e2220291, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35703615

RESUMO

INTRODUCTION: In several conditions, outcome stability is a great challenge for Orthodontics. Previous studies have reported that relapse commonly occurs along the years after orthodontic treatment finishing. OBJECTIVE: The aim of the present study was to evaluate in the long-term transversal dental arch changes of Class II division 1 patients treated with cervical headgear and fixed appliance. METHODS: Plaster study casts of 20 patients treated with cervical headgear without dental extractions were 3D-scanned and evaluated in three distinct times: initial (T1), immediate post-treatment (T2) and long-term retention (T3 - minimum 20 years). Transversal teeth distance of maxillary and mandibular canines, premolars and first molars were measured. RESULTS: A statistically significant increase during treatment was observed for all maxillary teeth transversal distances (p< 0.05). In turn, a significant reduction was observed in the long term (p< 0.05). For the mandibular teeth, canine transversal distance presented statistically significant constriction in the retention period (p< 0.05). Mandibular first molars distance was significantly expanded by treatment (p< 0.05) and remained stable in the long term. The changes observed for the other teeth or other times were considered not statistically relevant. CONCLUSIONS: For the accessed sample, transversal changes occurred during treatment and retention phases in Class II division 1 patients treated with cervical headgear and fixed appliance. Relapse was considered statistically relevant, even with the institution of a retention protocol.


Assuntos
Aparelhos de Tração Extrabucal , Má Oclusão Classe II de Angle , Dente Pré-Molar/cirurgia , Cefalometria , Humanos , Má Oclusão Classe II de Angle/diagnóstico por imagem , Má Oclusão Classe II de Angle/terapia , Recidiva , Resultado do Tratamento
16.
J Am Coll Surg ; 234(6): 1160-1165, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35703814

RESUMO

BACKGROUND: Laparoscopic and robotic ventral hernia repair with intraperitoneal mesh have been demonstrated previously to have comparable 30-day outcomes in the PROVE-IT randomized clinical trial. Here we report our 1-year follow-up of enrolled patients to examine exploratory outcomes. STUDY DESIGN: All patients enrolled in a previously published, registry-based, randomized trial investigating laparoscopic vs robotic ventral hernia repair with intraperitoneal mesh were reviewed. Several exploratory secondary outcomes were assessed: pain intensity (Patient-Reported Outcomes Measurement Information System [PROMIS 3a]), hernia-specific quality of life (Hernia-Specific Quality of Life Survey [HerQLes]), composite hernia recurrence, and reoperations. RESULTS: A total of 95% (71 of 75) follow-up was achieved: 33 laparoscopic repairs and 38 robotic repairs. Median follow-up time was 12 months [interquartile range 10 to 12 months]. Following regression analysis adjusting for baseline scores, there was no difference in postoperative pain intensity at 1 year (p = 0.94). However, HerQLes scores increased by 12.0 more points following robotic repairs compared to laparoscopic counterparts (95% CI 1.3 to 22.7, p = 0.03). Composite hernia recurrence was 6% (2 of 33) for the laparoscopic cohort and 24% (9 of 38) for the robotic group (p = 0.04). There was no difference in rates of reoperation (p = 0.61). CONCLUSIONS: Our exploratory analyses have identified potential differences in quality of life and recurrence, favoring the robotic and laparoscopic approaches, respectively. These findings warrant further study with larger patient cohorts to verify their potential significance.


Assuntos
Hérnia Ventral , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Hérnia Ventral/etiologia , Hérnia Ventral/cirurgia , Herniorrafia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Qualidade de Vida , Recidiva , Telas Cirúrgicas
17.
J Am Coll Surg ; 234(6): 1193-1200, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35703818

RESUMO

BACKGROUND: Although inguinal hernia repair in female patients is less common than in male patients, it remains a frequent procedure. The decision to divide or preserve the round ligament has largely been left to surgeon preference, but little data exists about its impact on outcomes. This study aimed to describe current practices for round ligament management and identify the impact of division on surgical and patient-reported outcomes. STUDY DESIGN: The 2013 to 2021 Abdominal Core Health Quality Collaborative database was queried for all female patients undergoing inguinal hernia repair with 30-day patient-reported outcome data available. Comparison groups were created based on round ligament management: round ligament division (RLD) or round ligament preservation (RLP). RESULTS: We identified 1365 female patients who underwent open (36.3%), laparoscopic (34.5%), or robotic (28.2%) repair. Most were non-recurrent (93%) and unilateral (82.6%). The round ligament was divided in 868 (63.6%) and preserved in 497 (36.4%) cases. There were no significant differences in overall complications (RLD 7.1%, RLP 5.2%, p = 0.17), reoperation (RLD 0.5%, RLP 0.2%, p = 0.4), or recurrence (RLD 0.1%, RLP 0.4%, p = 0.28). Mean European Registry for Abdominal Wall Hernias quality of life summary scores were not significantly different at 30 days (RLD 27.2, RLP 27.8) or 6 months (RLD 12.8, RLP 17.1). However, a significant difference was found in terms of mean pain-specific scores at 6 months, with lower pain scores in the RLD group (3 vs 4.7, p < 0.01), which persisted on multivariable analysis (p = 0.02). CONCLUSIONS: RLD is a common practice and is not associated with increased complications or recurrence. Although there is some evidence that RLD may result in decreased pain at 6 months, this must be balanced with potential functional complications of division that are not fully studied in this paper.


Assuntos
Hérnia Inguinal , Laparoscopia , Ligamentos Redondos , Feminino , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Humanos , Masculino , Dor/cirurgia , Qualidade de Vida , Recidiva , Ligamentos Redondos/cirurgia
19.
Med Oncol ; 39(8): 117, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35674832

RESUMO

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and relapsed B-ALL is the leading cause of mortality in children with leukemia due to a lack of response to treatment. S100A8 is a low molecular weight calcium-binding intracellular protein that is expressed in certain cells, and its increased expression is seen in most tumors as well as in relapsed childhood B-ALL cases. The present study indicates the important role of S100A8 in improving viability and resistance to chemotherapy in relapsed B-ALL lymphoblasts. S100A8 levels were compared in B-ALL and relapsed B-ALL lymphoblasts that were sensitive and resistant to Vincristine, respectively. S100A8 was inhibited in the lymphoblasts of two patients by antisense locked nucleic acid (LNA) GapmeRs and the decreased expression of S100A8 was evaluated using quantitative real-time PCR and ELISA. Then, the S100A8 antisense LNA GapmeRs-transfected cells were treated with Vincristine and the expression levels of S100A8 mRNA and S100A8 protein were re-determined. At all of these stages, cell viability and LC50 were assessed by MTT assay. The results showed that S100A8 levels in relapsed B-ALL lymphoblasts were significantly higher than B-ALL lymphoblasts. Moreover, the increase in S100A8 expression was proportionate to the increase in Vincristine resistance in these cells. The S100A8 knockdown procedure using antisense LNA GapmeRs decreased the cell viability and increased vincristine sensitivity in lymphoblasts of two patients, and it also increased the sensitivity to chemotherapy in relapsed B-ALL lymphoblasts. According to the findings of the present study, S100A8 is effective in developing lymphoblast resistance to chemotherapy, and its enhanced expression may contribute to shifting B-ALL into the relapse phase of the illness. As a result, S100A8 may be a valuable target for managing and improving relapses B-ALL.


Assuntos
Calgranulina A , Leucemia-Linfoma Linfoblástico de Células Precursoras , Calgranulina A/antagonistas & inibidores , Calgranulina A/genética , Criança , Humanos , Linfócitos/patologia , Oligonucleotídeos , Oligonucleotídeos Antissenso , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recidiva , Vincristina/farmacologia
20.
Sci Adv ; 8(23): eabj2820, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35675405

RESUMO

A notable number of acute lymphoblastic leukemia (ALL) patients develop CD19-positive relapse within 1 year after receiving chimeric antigen receptor (CAR) T cell therapy. It remains unclear if the long-term response is associated with the characteristics of CAR T cells in infusion products, hindering the identification of biomarkers to predict therapeutic outcomes. Here, we present 101,326 single-cell transcriptomes and surface protein landscape from the infusion products of 12 ALL patients. We observed substantial heterogeneity in the antigen-specific activation states, among which a deficiency of T helper 2 function was associated with CD19-positive relapse compared with durable responders (remission, >54 months). Proteomic data revealed that the frequency of early memory T cells, rather than activation or coinhibitory signatures, could distinguish the relapse. These findings were corroborated by independent functional profiling of 49 patients, and an integrative model was developed to predict the response. Our data unveil the molecular mechanisms that may inform strategies to boost specific T cell function to maintain long-term remission.


Assuntos
Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antígenos CD19 , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Proteômica , Receptores de Antígenos Quiméricos/metabolismo , Recidiva
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